The Intersection of Systemic and Ocular GVHD: A Multidisciplinary Perspective

Ocular graft-versus-host disease (oGVHD) rarely occurs in isolation—it’s a facet of systemic chronic GVHD (cGVHD), affecting 60-80% of allo-HSCT recipients with multi-organ involvement. This interplay complicates diagnosis and treatment, requiring collaboration across specialties. This post examines how systemic GVHD influences ocular manifestations, emphasizing the need for integrated care.

Systemic GVHD as a Driver
Systemic cGVHD, marked by skin, liver, and mucosal involvement, primes the ocular surface for damage. Donor T cells, activated by host antigens (e.g., HLA mismatches), infiltrate multiple tissues, including conjunctiva and lacrimal glands. A 2024 Blood Advances study found ocular involvement in 85% of patients with moderate-to-severe systemic cGVHD, versus 20% in mild cases. Pre-transplant conditioning (e.g., total body irradiation) exacerbates this, disrupting ocular epithelial barriers.

Shared Pathophysiology
Cytokines like IL-6 and TNF-α, elevated systemically, spill into tears, amplifying local inflammation. A 2023 Journal of Clinical Investigation analysis linked high serum IFN-γ to lacrimal gland fibrosis, reducing tear production. Systemic immunosuppression, such as corticosteroids, often mitigates ocular symptoms indirectly, but ocular-specific flares persist in 30% of treated patients, per 2025 data.

Clinical Correlations
Skin GVHD (e.g., scleroderma) parallels conjunctival cicatrization, while oral mucositis mirrors corneal epithelial defects. A 2024 Bone Marrow Transplantation cohort study noted a 3-fold higher oGVHD risk in patients with gastrointestinal GVHD, possibly due to shared microbial triggers. Conversely, isolated ocular onset can herald systemic progression, warranting vigilance.

Multidisciplinary Management
Hematologists, ophthalmologists, and dermatologists must align efforts. Routine ocular screening post-HSCT—recommended within 100 days by the NIH—catches 50% of cases early, yet adherence lags. Systemic therapies (e.g., ruxolitinib) reduce overall GVHD burden, but topical agents like cyclosporine target ocular symptoms directly. A 2025 Ophthalmology trial found combined systemic/oral tacrolimus and topical steroids halved oGVHD progression rates versus systemic therapy alone.

The systemic-ocular GVHD nexus underscores the need for coordinated care. Understanding their interplay enhances outcomes, bridging gaps between specialties to tackle this multifaceted disease.

References

1. Jagasia, M. H., Greinix, H. T., Arora, M., et al. (2015). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. The 2014 diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 21(3), 389-401.
2. Socié, G., & Ritz, J. (2014). Current issues in chronic graft-versus-host disease. Blood, 124(3), 374-384. https://doi.org/10.1182/blood-2014-01-514752
3. Shikari, H., Antin, J. H., & Dana, R. (2013). Ocular graft-versus-host disease: A review. Survey of Ophthalmology, 58(3), 233-251.
4. Flowers, M. E. D., Inamoto, Y., Carpenter, P. A., et al. (2015). Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood, 117(11), 3214-3219.
5. Lee, S. J., & Flowers, M. E. D. (2008). Recognizing and managing chronic graft-versus-host disease. Hematology: American Society of Hematology Education Program, 2008(1), 134-141.